For Patients

Haemoglobin is the substance that colours blood red and carries oxygen to all major organs. To produce haemoglobin, in combination with iron that we consume through our diets, our bodies make proteins called porphyrins.

In people with porphyria, there is a deficiency of an enzyme along the haem biosynthesis pathway, which results in an over-production of porphyrins.

There are two types of porphyrias: the first type is the acute porphyrias and are characterised by acute attacks. Some of them include cutaneous manifestations. The other types are the cutaneous porphyrias. These involve a build-up of porphyrins in the skin. They are sensitive to sunlight and result in painful sores and blisters.

Acute porphyrias always present in the form of “acute attacks”. During an acute attack, excess porphyrins build up inside the body and give rise to unpleasant symptoms. The onset of the attack is rapid (over a few hours) and it lasts for a relatively short period of time (a few days or more). The excess porphyrins and porphyrin precursors are tested during an attack, to diagnose the condition.

Misdiagnosis is common, as symptoms of an attack are not unique to the condition. Also, without proper intervention, these severe attacks can be very dangerous and even fatal.

“As a teenager, I began to have extremely severe abdominal pain and rapid pulse and I even had a little bit of confusion, but this pain was so severe that I’d never felt anything like it. I was doubled over in pain.”

“I suffered from quite severe paralysis, which tended to start around my hands and fingers, toes and feet and working its way up my legs and arms until eventually I had complete paralysis.”

Acute porphyria is a rare condition and it is usually diagnosed during an acute attack.

These tests must be carried out as soon as possible after the onset of an acute porphyria attack, as the concentrations of porphyrins and porphyrin precursors may reduce quickly after an attack. Therefore, if samples are not taken at the correct time, acute porphyria may be missed.

There is one simple diagnostic ‘test’ that can aid diagnosis – the colour of the patient’s urine sample on exposure to light. If the urine turns dark on exposure to sunlight (after approx. 30 minutes), this may indicate that the patient is experiencing the onset of an acute attack. It must be noted that this test may not work 100% of the time. Further tests should be carried out on urine, blood and stool samples to confirm the diagnosis and to identify which type of acute porphyria is present.

“There was one particular doctor who came out to see me and saw the dark urine and said: “I think I’d like to investigate two things”, one of them was porphyria.”

It is a rare condition, with about 1 in 75,000 people in European countries affected by the most common type of porphyria.1 Most people with acute porphyria never experience any health problems, but less than 1 in 5 will experience an acute attack.2 Females are more likely to suffer than males and the most common age for an attack to occur is between late teens and early 40s.

“Porphyria, it may be rare but someone has it and that someone might be you.”

Acute porphyria is inherited (passed down through genes), usually from one parent and rarely from both patents. Most people who inherit a faulty gene won’t suffer an acute attack, as the condition is often latent. The gene can be passed through the generations without an individual realising that it is present in the family, until someone has an acute attack.

There is currently no way of predicting who will suffer from an acute attack, however, it is recommended that family members of sufferers are screened for the gene through molecular testing. This means that all those at risk of an acute attack can be identified.

“Because my sister had the condition and because we had family awareness, I had genetic testing at the age of 16, so I knew I had the gene. The fact that I knew I had the gene meant that I knew what kind of treatment I needed.”

“For porphyria patients, those who know the most, do the best. ”

Acute attacks can be triggered by alcohol, medications and very low calorie diets. Variations in hormone levels are also a common factor, which is why females tend to experience more attacks than males.

“I follow very closely the safe and unsafe drug list.”

“No hormones, no hunger.”

For HCPs

Porphyrias are a group of metabolic disorders that result from a specific deficiency of one of the eight enzymes along the haem biosynthesis pathway. This deficiency results in an accumulation of haem porphyrins, which may lead to clinical manifestations.5Porphyrias are also classified as hepatic or erythropoietic, based on the organ system in which haem precursors are overproduced.6Porphyrias are generally either autosomal dominant (AD) or autosomal recessive (AR).

One of the eight main forms of porphyria will occur, depending on which of the enzymes is defective. They are classified according to the type of illness they cause.5 Acute disease is characterised by episodic acute neurovisceral attacks and non-acute disease is characterised by light-sensitive lesions but without acute attacks.

The acute porphyrias are inherited metabolic disorders of haem biosynthesis in which specific patterns of accumulation of haem precursors are associated with specific clinical manifestations.6

Haem is required for the synthesis of haemoproteins like haemoglobin and myoglobin, which play important roles in oxidation-reduction reactions and oxygen transport.5

In acute porphyria, specific enzymes within the haem biosynthesis pathway are defective.

An acute porphyria attack occurs when the requirement for haem is increased to the point where the defective enzyme becomes rate-limiting. This leads to an accumulation of porphyrins and porphyrin precursors (such as ALA and PBG) on the haem biosynthetic pathway (Figure 2).

The exact mechanisms underlying acute attacks are not yet well understood, however, the leading hypothesis is that during an attack, ALA and/or PBG overproduced by the liver are neurotoxic.6

Figure 2. The haem biosynthetic pathway, indicating the enzymes and intermediates responsible for haem synthesis and the form of porphyria, which results from deficiency of that particular enzyme. Human hepatic porphyrias are in the green boxes. Adapted from Karim et al. 2015.

This is the most common type of porphyria. In Europe, the incidence has been estimated as 1 in 75,000.1

Symptoms of an AIP attack and their severity vary greatly, but the skin is never affected. The majority of people make a full recovery from an attack, although about 1 in 10 people will suffer a repeat attack.5

People with VP are at risk of both acute attacks and experiencing skin problems, though not necessarily at the same time. The prevalence of VP depends on location. In Europe, it is half as prevalent as AIP.

Skin disease is present in approx. 40% of patients with VP, whereas acute attacks are present in approx. 10%. VP is an autosomal dominant disorder which presents in both males and females and usually only becomes expressed after puberty.10

HCP is about seven times less common then AIP1 and the major difference is that people with HCP can have acute attacks at the same time as skin problems.

This type is sometimes called plumboporphyria and is extremely rare, but is similar in outlook to AIP. The severity of the condition as a whole may vary.10

The cause of neurological dysfunction in acute porphyrias has not been determined, however, there is evidence for a direct toxic effect of 5-aminolevulinic acid (ALA) on the neuron and a possible indirect effect of haem deficiency within the neuron.10 Research has also shown that both symptomatic and latent patients are more likely to suffer from chronic renal failure with progressive tubulointerstitial nephropathy and hepatocellular carcinoma (HCC).6

“Doctors should really pay attention to someone with abdominal pain.”

Acute porphyrias are very rare conditions and as the symptoms are non-specific, they are often misdiagnosed.7, 13

Incorrect diagnosis may lead to inappropriate treatments and the use of unsafe medication, and possible inappropriate interventions (e.g. exploratory abdominal surgery). These actions may aggravate the attack and lead to serious neurological complications.

An acute attack of porphyria should be suspected in any patient with moderate to severe pain and a soft abdomen, especially when accompanied by an increased pulse rate and high blood pressure.10

Acute attacks of porphyria always result in an increased urinary excretion of the porphyrin precursors porphobilinogen (PBG) and ALA, but ALA is generally not measured in most laboratories and requires specialist interpretation. The first line diagnostic step is a PBG test on a urine sample. It is important that the urine sample is taken during an acute attack so that the diagnosis is not missed.14, 15

The next step is the identification of the specific porphyria. When analysing porphyrin type, no single test is uniformly applicable. As each porphyrin varies in its water solubility, some accumulate in the urine, whereas others will appear in the stool. Porphyrins may also accumulate in certain patterns in plasma. Therefore, patients are required to submit blood, urine and stool samples for testing.10

In an emergency setting, the patient should be stabilised before this occurs. The test requires a sample of EDTA preserved blood and a small faeces sample. These samples are generally sent to a specialist, accredited porphyrin laboratory. These laboratories have the facilities to perform both plasma porphyrin fluorescence emission scanning and to determine the faecal coproporphyrin isomer ratio (FCR). The plasma scan is used to distinguish VP from AIP. Once VP is excluded, the FCR can distinguish AIP from HCP.

Retrospective diagnoses are more complicated due to possible PBG concentration depletion.14, 15

Molecular testing is also extremely important in porphyria diagnosis, but is rarely appropriate in the initial diagnosis stage. It allows a patient to be assigned with a particular genetic mutation. This information can then be used to screen family members and detect carriers. Although many carriers may never present symptoms clinically, it is still important to identify possible carriers.10

“The first hypothesis was shingles and my symptoms were treated accordingly, but with time the pain worsened and passed through my chest. ”

“I think it’s important particularly that the doctors know more about it and are aware of it. Testing for porphyria is very important.”

Videos

Think Porphyria

Patient Stories

Karina

Liz

Sue

Sue B

Desiree

Jessica - HCP

Jessica - Journey To Diagnosis

John

“I had horrible
abdominal pain.”

Desiree, Acute Intermittent Porphyria Patient

“Because my sister had the condition and because we had family awareness, I had genetic testing at the age of 16, so I knew I had the gene. The fact that I knew I had the gene meant that I knew what kind of treatment I needed.”

Sue, Acute Intermittent Porphyria Patient

"I suffered from quite severe paralysis, which tended to start around my hands and fingers, toes and feet and working its way up my legs and arms until eventually I had complete paralysis.”

Liz Gill, Acute Intermittent Porphyria Patient

“I think it’s important particularly that the doctors know more about it and are aware of it. Testing for porphyria is very important.”

Orphan Europe

A unique pharmaceutical company

Orphan Europe, part of the Recordati group, is a unique pharmaceutical company focusing on the research and development of orphan medicinal products. Since 1990 we have used big thinking and extensive know-how on behalf of people affected by rare diseases. Patients and their families are central to our planning, our thinking and our actions. Recordati orphan drugs is present in the USA through its company Recordati Rare Diseases.

Big thinking for people with rare diseases

Orphan Europe is a leading orphan drug company since 1990: 19 product references sold in 2014

Over 130 staff in 15 countries. Headquarters in Paris La Défense and distribution centre in Nanterre

Infrastructure developed to novel needs of developing, producing, packaging and distributing very small numbers of specialist products to people around the world

Dedicated to finding new treatments and improving the lives of people with rare diseases

Extensive experience in the metabolic field, but also oncology and other rare diseases

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